Anthrax Lethal Factor as an Immune Target in Humans and Transgenic Mice and the Impact of HLA Polymorphism on CD4 T Cell Immunity

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Anthrax is of concern with respect to human exposure in endemic regions, concerns about bioterrorism and the considerable global burden of livestock infections. The immunology of this disease remains poorly understood. Vaccination has been based on B. anthracis filtrates or attenuated spore-based vaccines, with more recent trials of next-generation recombinant vaccines. Approaches generally require extensive vaccination regimens and there have been concerns about immunogenicity and adverse reactions. An ongoing need remains for rationally designed, effective and safe anthrax vaccines. The importance of T cell stimulating vaccines is inceasingly recognized. An essential step is an understanding of immunodominant epitopes and their relevance across the diverse HLA immune response genes of human populations. We characterized CD4 T cell immunity to anthrax Lethal Factor (LF), using HLA transgenic mice, as well as testing candidate peptide epitopes for binding to a wide range of HLA alleles. We identified anthrax epitopes, noteworthy in that they elicit exceptionally strong immunity with promiscuous binding across multiple HLA alleles and isotypes. T cell responses in humans exposed to LF through either natural anthrax infection or vaccination were also examined. Epitopes identified as candidates were used to protect HLA transgenic mice from anthrax challenge.

Vyšlo v časopise: Anthrax Lethal Factor as an Immune Target in Humans and Transgenic Mice and the Impact of HLA Polymorphism on CD4 T Cell Immunity. PLoS Pathog 10(5): e32767. doi:10.1371/journal.ppat.1004085
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004085

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